tbuckley/cabot-search huggingface dataset:
Radiation fractionation effect on IDO1 through NF-kB/COX2 axis in non-small cell lung cancer.
Authors: Yanli Lan, Wenhu Pi, Zhangjie Zhou, Dan Mei, Yixiu Xu, Xinhang Xia, Wei Wang, Haihua Yang, Feng-Ming (Spring) Kong
Journal: Journal of Clinical Oncology (2023)

e20613 Background: Lung cancer is the leading cancer mortality worldwide. Radiotherapy(RT) plays an important role in lung cancer treatment. Different does fractionation of RT has different effects on the prognosis of lung cancer. For example, stereotactic body radiotherapy can significantly improve the prognosis compared with conventionally Fractionated Radiotherapy. In non-small cell lung cancer, we have previously shown that Indoleamine 2,3-dioxygenase 1 (IDO1) metabolites and radiation induced changes had significant effects on long-term survival in patients treated with either Stereotactic body Radiation Therapy of 10Gy fraction size or conventional fractionated radiotherapy of 2Gy fraction size. However, the underlining molecular mechanism is unknown. In this study, we aimed to elaborate the molecular mechanism of such clinical differential effects in the laboratory. Methods: This study applied two dose/fractionation regimens with a similar BED10: 10Gyx1 and 2Gyx8. 10Gyx1 and 2Gyx8 were tested in cell lines of A549, H1299, Calu-1, TC-1 of human and murine NSCLC as well as normal rat cardiomyocyte cell line H9c2, and in vivo (TC-1 implanted C57Bl/6 mice). The mRNA and protein levels of IDO1, p-NF-kB, COX2 from cells and tumor tissues were determined by using qPCR, western blot and immunohistochemistry. Survival outcome was tested by colony formation assay in vitro and tumor growth curve in vivo. Results: In vitro, 10Gyx1 and 2Gyx8 induced IDO1 expression in all tested cell lines and the level of IDO1 expression induced by 10Gyx1 was lower than 2Gyx8. Both 10Gyx1 and 2Gyx8 increased p-NF-kB and COX2 expression and the level induced by 10Gyx1 was lower than 2Gyx8. In tumor bearing mice, two dose/fractionation regimens also induced intratumor IDO1 expression and increased the levels of p-NF-kB and COX2. Interestingly, the increased levels of IDO1, p-NF-kB, COX2 after 10Gyx1 were also significantly lower than 2Gyx8 in vivo. IDO inhibitor synergized with RT and enhanced cell killing efficacy of RT. Conclusions: The findings of this study suggest different does fractionation of RT induced up-regulation of IDO1 through NF-kB/COX2 axis in NSCLC and non-cancerous cell lines, what’s more, hypofractionated radiotherapy 10Gyx1 had less upregulation that of conventionally fractionated radiotherapy 2Gy x8 on IDO1 immune inhibitory pathway. The finding of hypofractionated radiotherapy less immune suppression differ from the traditional belief of more immune stimulation. Our current study provides a rationale in using IDO1 as a biomarker to design RT dose fractionation and/or immunotherapy in combination and possibilities for clinical trials to design IDO1 inhibitors in combination with radiotherapy.
Exploring the association between medical marijuana cardholder status and antiemetic overuse.
Authors: Alan Baltz, Cheng Peng, Laura Elisabeth Gressler, Sajjad Akbar Bhatti, Kanna Lewis
Journal: Journal of Clinical Oncology (2023)

e18812 Background: The conscientious prescribing of antiemetics by chemotherapy-induced nausea and vomiting (CINV) risk was highlighted in the American Society of Clinical Oncology (ASCO) “Choosing Wisely” recommendations. The pharmacologic properties of medical marijuana (MMJ) and increased availability through legislation may allow for decreased incidence of CINV, however, little is known about the effects of MMJ legislation on the use of antiemetics. The objective is thus to assess the association between MMJ cardholder status in Arkansas and antiemetic overuse among cancer patients. Methods: A retrospective cohort was derived from the linked Arkansas All Payers Claims Database (APCD; 2013-2020) and MMJ card holder data (2013-2019). The cohort of interest consisted of individuals aged 18 and older with a chemotherapy claim in outpatient setting within 12 months of a cancer diagnosis. Exposed individuals had access to MMJ through an MMJ card. The primary outcome of interest was antiemetic overuse, as characterized by the ASCO recommendation. Antiemetic use was identified using prescription claims and coded as present if an antiemetic prescription was identified between two weeks prior to two days following chemotherapy receipt. Logistic regression, adjusted for baseline demographic and prescription characteristics, were used to calculate the adjusted odds ratios (aOR) and 95% confidence intervals (CI) of experiencing antiemetic overuse. Results: Within Arkansas, 22,139 individuals without a MMJ card received 167,084 chemotherapy cycles and 161 individuals with a MMJ card received 2,775 chemotherapy cycles. Antiemetic overuse was identified in 6.59% versus 5.87% of chemotherapy cycles among non-MMJ cardholders and MMJ cardholders respectively. The calculated aOR of antiemetic overuse among individuals with a MMJ card was .671 (95%CI:.567-.794) when compared to individuals without a MMJ card. Conclusions: The findings indicate that MMJ cardholders are significantly less likely to experience antiemetic overuse than individuals without MMJ cards. Increased awareness of ASCO’s recommendation and further investigation into the use, effectiveness, and safety of cannabis for the use of CINV mitigation is needed to inform patient and provider decision-making.
The impact of lymphadenectomy on survival outcomes of ovarian clear cell carcinoma: A systematic review and meta-analysis.
Authors: Yan Liu, Kun Song, Changzhen Huang, Ran Chu
Journal: Journal of Clinical Oncology (2023)

e17572 Background: The treatment strategies for ovarian clear cell carcinoma (OCCC) are the same as those for epithelial ovarian cancer. Due to the rarity of OCCC, no prospective studies of its surgery have been reported. Therefore, the therapeutic significance of lymphadenectomy for OCCC needs to be further clarified. Methods: The Web of Science, Scopus, PubMed, and other sources (e.g. Google Scholar) were searched from each database’s earliest inception to June 2021. English-language publications of observational studies that investigated the role of lymphadenectomy in patients with OCCC were included.The pooled hazard ratio (HR) and 95% confidence interval (CI) were calculated. Results: The analysis demonstrated that lymphadenectomy is associated with significantly improved disease-specific survival (DSS) (HR = 0.76; 95%CI = 0.60-0.95; P = 0.02; I 2 = 0.0%) and disease-free survival (DFS) (HR = 0.58; 95%CI = 0.33-1.00; P = 0.05; I 2 = 61%), but not for overall survival (OS) (HR = 0.80; 95%CI = 0.60-1.06; P = 0.12; I 2 = 19%) and progression-free survival (PFS) (HR = 0.95; 95%CI = 0.64-1.42; P = 0.79; I 2 = 0.0%). But it is worth noting that several single studies indicated a tendency of improved OS, PFS, DFS, DSS with lymphadenectomy. The discrepancy of different results from similar studies should be viewed with caution. Conclusions: Lymphadenectomy could not significantly improve OS and PFS for OCCC, but is associated with improved DFS and DSS. Gynecologic oncologists should tailor treatment to patients to achieve optimal outcomes. Lymph node metastasis should be detected as accurately as possible before and during surgery to identify patients who can benefit from lymphadenectomy. The establishment of an international OCCC database and the development of multicenter clinical studies with international cooperation will help improve the treatment strategy.
Associations of employment disruptions and financial hardship among individuals diagnosed with cancer in the US.
Authors: Michael T. Halpern, Janet De Moor, Xuesong Han, Jingxuan Zhao, Zhiyuan Zheng, Robin Yabroff
Journal: Journal of Clinical Oncology (2023)

12097 Background: Financial hardship is experienced by approximately half of working-age individuals diagnosed with cancer. Many working individuals diagnosed with cancer also experience disruptions with their employment. This study examines whether employment disruptions are associated with financial hardship among individuals diagnosed with cancer in the US. Methods: We utilized data from the 2016/2017 Medical Expenditure Panel Survey (MEPS) Experiences with Cancer self-administered questionnaires and identified individuals diagnosed with cancer at age &gt;18 who worked for pay at the time of or following their cancer diagnosis. Employment disruption was defined as taking extended paid time off work; switching to a part time or less demanding job or to a flexible work schedule; and/or retiring early due to cancer, cancer treatment, or late effects. Financial hardship was defined in 3 domains: material (borrowing money, financial sacrifices, or being unable to cover medical costs); psychological (worrying about medical bills, financial stability, keeping job/income, or future earnings); and behavioral (delaying/forgoing medical care because of cost). Multivariable logistic regression analyses adjusting for the MEPS survey design were used to determine associations of employment disruption due to cancer with any financial hardship and with financial hardship intensity while controlling for patient demographic, health insurance, and clinical characteristics. Results: Among 732 individuals with a cancer history, 47.4% experienced employment disruptions and 55.9% experienced any financial hardship. Financial hardship was significantly more common among cancer survivors with employment disruptions than without disruptions (68.7% vs. 44.5%; p-value of difference &lt; 0.0001). Findings were consistent across multiple hardship measures/domains and across years since last cancer treatment. In multivariable logistic regression analyses, cancer survivors with employment disruptions were significantly more likely to have greater (OR = 2.8; 95% CI 2.0, 3.9) financial hardship intensity. Individuals of race/ethnicity other than non-Hispanic White; who had Medicare (vs. private) insurance and were age &lt; 65 years old at diagnosis; or had breast, colon, or prostate cancer (vs. melanoma reference group) were also more likely to experience financial hardship. Older individuals and those who were married were less likely to experience financial hardship. Conclusions: Employment disruptions are common and significantly associated with multiple types of financial hardship among cancer survivors. Employer workplace accommodation and other policies to minimize disruptions among individuals diagnosed with cancer may reduce financial hardship in this vulnerable population.
Anlotinib combined with carboplatin/paclitaxel and maintenance anlotinib as front-line treatment for newly diagnosed advanced ovarian cancer: A phase II, single-arm, multicenter study (ALTER-GO-010).
Authors: Yi Jiang, Yingchun Gao, Huaijun Zhou, Yulang Cai, Jinjin Yu, Youguo Chen, Jinling Xue, Wenjun Cheng
Journal: Journal of Clinical Oncology (2023)

5575 Background: Several studies have shown that antiangiogenic drug combined with chemotherapy as first-line treatment, followed by antiangiogenic drug maintenance therapy significantly improve outcomes for patients with ovarian cancer. Anlotinib, a highly effective VEGFRs, FGFRs, PDGFRs and c-kit multi-target tyrosine kinase inhibitor, has been approved for multiple tumor types in China. The aim of this single arm, multicentric, phase II study is to investigate the efficacy and safety of using anlotinib combined with carboplatin/paclitaxel as front-line treatment for advanced ovarian cancer patients. Methods: Eligible patients with FIGO stage III–IV primary epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer and ECOG PS 0-1 undergo primary cytoreductive surgery or interval debulking surgery, will receive 6-8 cycles of chemotherapy (paclitaxel 175 mg/m2 + carboplatin area under the curve [AUC] 5 q3w) and anlotinib (12 mg po qd, days 1-14, 21 days per cycle, anlotinib will be omitted from the first treatment cycle to prevent delayed wound healing). After chemotherapy finished, anlotinib continues as maintenance monotherapy until disease progression, unacceptable toxicity, or death. Patients with prior anti-angiogenic therapy or major surgical procedure within 28 days before starting anlotinib therapy will be excluded. The primary endpoint is progression free survival (PFS). Key secondary endpoints include overall response rate, disease control rate per RECIST1.1, overall survival, safety. Results: From 9 Sep 2021 to 30 Jan 2023, 30 pts were enrolled, including 96.7% (29/30) high-grade serous carcinoma (HGSC) and 3.33% (1/30) endometrioid carcinoma (EC). The median age was 56 years old, with 96.7% (29/30) patients in FIGO stage III and 3.33% (1/30) in stage IV Median follow-up was 5.36 (95% CI: 3.68, - 7.98) months. PFS rates at 6 months and 9 months were both 100%. Twenty-nine patients (96.7%) experienced adverse events (AE) of any level. The most common AEs include white blood cell decreased, neutrophil count decreased, anemia, platelet count decreased, lymphocyte count decreased and hypertension. There was no treatment-related death during the study. Conclusions: Preliminary results of anlotinib combined with carboplatin/paclitaxel have shown favorable efficacy and tolerated safety profile in newly diagnosed advanced ovarian cancer patients. Clinical trial information: NCT04807166 .
Tumor-informed circulating tumor DNA (TI-ctDNA) based molecular residual disease (MRD) detection and relapse risk for patients with stage II-IV melanoma in surgical remission: A single center experience.
Authors: Logan Rhea, Megan Daniels, Roy Sabo, Andrew Stewart Poklepovic
Journal: Journal of Clinical Oncology (2023)

9572 Background: Melanoma is associated with significant risk of relapse after surgery. While the odds of relapse increase with advancing stage, long term relapse free survival (RFS) is possible without adjuvant therapy in a significant subset of patients as shown by AJCC v8 staging long term survival data. TI-ctDNA (Signatera™) is a non-invasive biomarker for MRD detection and functions by sequencing the patient’s own tumor for the creation of a customized panel of PCR probes based upon a tumor’s unique mutational profile. Positive TI-ctDNA testing is significantly associated with relapse after surgical resection in colorectal cancer and may help inform treatment decision-making, allowing for intensification or de-intensification of patient management. This study describes the operating characteristics of TI-ctDNA in monitoring for relapse in patients with resected melanoma. Methods: This is a single center retrospective analysis of patients with stage IIb-IV melanoma in surgical remission. Between January 2021 and January 2023, male and female patients presenting in surgical remission were monitored with TI-ctDNA at 6- or 12-week intervals. Surveillance imaging for relapse was performed according to standard of care guidelines appropriate for tumor stage. Patients were treated with immunotherapy, targeted therapy, or melanoma specific anti-tumor vaccine. Duration of RFS from surgery to detectable TI-ctDNA was recorded, along with duration of RFS from surgery to confirmed melanoma relapse. Results: 45 eligible patients were included in the analysis. 10 patients had detectable TI-ctDNA during the study period. 7 patients had confirmed relapse, 6 of whom were TI-ctDNA positive and 1 who was TI-ctDNA negative. The total relapse rate in TI-ctDNA positive patients (6/10) was significantly higher than the relapse rate in TI-ctDNA negative patients (1/35) [p = 0.0002]. Time to detection of positive TI-ctDNA was variable and ranged from 0 to 664 days (median 73 days). Conclusions: TI-ctDNA testing demonstrated preliminary ability to differentiate melanoma patients at the highest risk of relapse. Prospective evaluation of TI-ctDNA monitoring for determination of patients at high versus low risk of relapse is warranted and may help to inform future clinical trial designs by allowing for patient stratification to low risk (undetectable TI-ctDNA) and high risk (detectable TI-ctDNA) disease states.
Socioeconomic factors associated with a late-stage multiple myeloma diagnosis: An analysis of the National Cancer Database.
Authors: Chirag Patel, Liam P. Townley, Peter T. Silberstein, Jillian Marie Gallegos
Journal: Journal of Clinical Oncology (2023)

e20036 Background: Multiple myeloma is an aggressive monoclonal plasma cell proliferative disorder that is the second most common hematologic malignancy. On a global scale, multiple myeloma led to an estimated 106,000 deaths in 2018 alone. The exact cause of multiple myeloma is not well understood. Later stage of diagnosis is correlated with worse outcomes; thus, it is critical to assess the socioeconomic factors associated with diagnosis at early versus late stages. Methods: Using the National Cancer Database, we aimed to identify associations between socioeconomic factors of patients that present with Revised International Staging System (R-ISS) stage I multiple myeloma in comparison to R-ISS stage III at diagnosis. In this study, 5,512 patients from the National Cancer Database who were diagnosed with R-ISS stage I and stage III multiple myeloma were analyzed based on age, ethnicity, race, education, insurance type, income, education, geographic location, facility type, sex, Charlson-Deyo score, and urban or rural setting. Demographic factors of patients that presented with stage I and stage III disease were analyzed using chi square, ANOVA, and multivariate analyses. All patients included in the study were diagnosed with multiple myeloma between 2004 and 2020. Results: We identified significant (P &lt; 0.05) associations between insurance type, median income, education, rural setting, and Charlson-Deyo score with diagnosis of R-ISS stage III multiple myeloma. For insurance type, private insurance, other government insurance, and Medicaid had lower percentages of R-ISS stage III diagnosis than patients without insurance (P &lt; 0.001). Medicaid and over government insurance were up to 70% less likely to present with stage III MM than patients without insurance (P &lt; 0.001). Regarding income and education, patients from a zip-code associated with an income of &lt; $38,000 and zip-codes with lower levels of high school diploma had higher rates of stage III multiple myeloma diagnosis (P &lt; 0.001). Patients from completely rural or less than 2,500 urban population adjacent to a metro area (P &lt; 0.005) and not adjacent to a metro area (P &lt; 0.025) showed significant increase in later stage multiple myeloma diagnosis than those from a metro setting with population above one million. Patients with Stage III at presentation were older than patients with stage I on average (P &lt; 0.001). There were no significant differences seen based on race, sex, ethnicity, or region in the United States. Conclusions: Factors associated with increased likelihood of later stages of diagnosis of multiple myeloma include insurance type, median income, education, and rural location. Future analysis should further investigate the specific barriers to early patient diagnosis and treatment due to insurance type, education level, and rural setting.
Racial disparities in survival and stage at diagnosis among adolescent and young adult patients with cancer.
Authors: Kekoa A. Taparra, Kāʻeo Kekumano, Ryan Benevente, Megan Y. Gimmen, Connon Kinslow, Curtiland Deville, Erqi L. Pollom
Journal: Journal of Clinical Oncology (2023)

6615 Background: Adolescent and young adult (AYA) patients (15-39 years) are an underrecognized population with high risk of select malignancies. Compared to pediatric and adult patients, AYA patients have not achieved improvements in cancer survival. No studies have evaluated overall survival (OS) and stage at diagnosis among all 5 federally recognized races in the US. Here we aim to investigate OS and stage at diagnosis among AYA patients by race. Methods: A retrospective cohort study of AYA patients diagnosed between 2004-2017 was conducted with the National Cancer Database. Patients with the 10 deadliest AYA cancers with at least 6 months of follow-up were included. Primary endpoints were OS (time from diagnosis to death) and late stage at diagnosis (stage III/IV or Grade III/IV for central nervous system [CNS] cancer). Kaplan-Meier estimates and log-rank tests assessed OS. OS and late stage were evaluated by race using multivariable Cox proportional hazard (adjusted hazard ratio [aHR]) and logistic (adjusted odds ratio [aOR]) regressions, respectively, with 95% confidence intervals (95%CI). All regressions were adjusted for sociodemographic and cancer characteristics. Results: 291,899 AYA patients were included: 64% female, 65% stage I/II, and 62 month median follow-up. Cancer sites included 27% breast, 16% lymphoma, 13% melanoma, 11% testis, 9% CNS, 7% colorectal, 7% cervix, 5% sarcoma, 3% ovary, and 2% lung. Race included 82.3% Non-Hispanic White (NHW), 14.0% Black, 2.9% Asian, 0.5% American Indian and Alaska Native (AIAN), and 0.3% Native Hawaiian and other Pacific Islander (NHPI). OS differed for all cancers by race (p&lt;.0001), except for lung (p=.008), CNS (p=.32), and ovary (p=.28). OS was significantly inferior for NHPI, Black, and AIAN but superior for Asian, versus NHW (Table). NHPI had inferior OS (aHR, 95%CI) for melanoma (4.5, 2.0-10.0), colorectal (1.8, 1.3-2.4), lymphoma (1.7, 1.1-2.1), and cervix (1.6, .1-2.4) cancers. Black patients had inferior OS for melanoma (1.6, 1.2-2.2), lymphoma (1.5, 1.4-1.6), and breast (1.4, 1.3-1.4) cancers. Asian patients had superior OS for breast (0.7, 0.7-0.8) and lung (0.7, 0.6-0.9) but inferior survival for testis (1.9, 1.3-2.9) cancers. AIAN patients had inferior OS for colorectal (1.4, 1.0-1.9). Late stage at diagnosis was higher for NHPI, Black, and Asian patients, compared to NHW patients (Table). Conclusions: Both NHPI and Black AYA patients with cancer have higher risk of death and late stage disease at diagnosis, compared to NHW patients. Our data reveal racial disparities among Indigenous AYA patients masked by prior data omission. [Table: see text]